. 2010 Oct 15;6(5):491–509.

Appendix.

First Author Reference Evidence Level	Disorder/Patient No.	Design	Titration	Equipment/Pressure	Outcome/Findings (abbreviations at end of table)
Ambrogio⁹ 2009 Randomized Crossover Level I Average Volume Assured Pressure Support (AVAPS) vs BPAP	Chronic hypercapnic respiratory failure using NPPV OHS (with/ without OSA) COPD NMD N = 28	3 PSGs 1. Prescription-Validation BPAP titration to validate chronic NPPV settings IPAP-T = chosen IPAP level from BPAP titration 2.AVAPS or BPAP treatment 3.Crossover to alternate treatment	BPAP titration with PSG start BPAP = 8/4, titrate to eliminate obstructive events (apnea, hypop, FL) IPAP increased in 2 cm increments when suspected hypoventilation (SaO₂ < 90% for 3 minutes) in absence of obstructive events	AVAPS IPAPmax = 30 or IPAP chosen for IPAP-T + 10 IPAPmin = IPAP-T - 5 AVAPS tidal volume goal either 8 cc/kg or 110% of calm tidal breathing (patient preference)	Equivalent sleep quality on AVAPS and BPAP Higher minute ventilation on AVAPS
Banerjee¹⁷ 2007 Case Series Level IV	Prospective study of patients with BMI ≥ 50kg/m2 undergoing PSG group 1: OSA AHI = 61.2/hr N =23 group 2: OSA+OHS OSA + PCO₂ > 45 mmHg without lung disease N = 23	PSG #1 Diagnostic,if AHI ≥ 15/hr then CPAP PSG 2^nd PSG with CPAP measurements during CPAP trial	Manual PSG CPAP titration with auto-CPAP device CPAP titrated to normalize inspiratory flow pattern Once flow trace had normalized CPAP was increased by no more than 3 cm H₂O in attempt to improve SaO₂	CPAP values mean CPAP (cm H₂O) OSA group 12.9 OHS group 13.9	AHI group 1: OSA AHI = 61.2/hr group 2: OSA+OHS AHI = 78/hr Baseline PCO₂ group1: OSA PCO₂ = 42.9 mmHg group1: OSA+OHS PCO₂ = 54.3 mmHg In both groups CPAP improved AHI, REM duration, arousal indices, nocturnal desaturation Once obstructive events eliminated: 9% of OSA and 43% of OHS had >20% TST with SaO₂ less than 90%
Berger¹³ 2001 Retrospective Case Series Level IV	OHS 49 retrospectively identified 23 came for follow-up	PSG for Dx PSG for PAP titration --> ultimate Rx depends on response to CPAP during the titration group 1 treated with CPAP group 2 treated with BPAP	PSG titration: 1. CPAP increased to eliminate obstructive events 2. If SaO₂ < 90% + flow limitation, CPAP increased If effective --> group 1: CPAP Rx (noncompliant had trach) 3. If SaO₂ < 90% when no Flow limitation: group 2 BPAP used (noncompliant had trach + volume vent)	group1: 11 patients CPAP Rx CPAP 13 cm H₂O group 2: 12 patients BPAP Rx IPAP 18 cm H₂O range (12 to 25) cm H₂O EPAP 8 range ( 3 to 14)	Compliant patients had drop in daytime PCO₂ to near normal values – in both groups group 1: [CPAP / trach] group 2: [BPAP / trach + volume ventilator] groups
Bourke³⁹ 2003 Case series Level IV	ALS patients N = 22	ALS group followed Quality of life measures every 2 months PSG every 4 months in group with ALS Those meeting criteria were offered NPPV Analysis: comparison of Pre-NPPV measures with post- NPPV measures	NPPV started in Hospital BPAP adjusted on basis of nocturnal oximetry and daytime ABGs, + compliance 15 tried NPPV 10 continued NPPV	nasal, oro-nasal, total face masks, mouthpieces BPAP in ST mode mean values: IPAP = 16 EPAP = 4 backup rate not specified Asynchrony due to leaks controlled by limiting IPAPmax	NPPV associated with improved quality of life Survival correlated with compliance to NPPV orthopnea best indicator of benefit from NPPV and adherence (better than AHI, nocturnal symptoms, PCO₂)
Bourke³ Lancet Neuro 2006 Randomized Controlled Trial Level I with respect to NPPV vs Standard care	ALS patients NPPV N = 22 standard care N = 19 20 normal or mild impairment of bulbar function 21 severe bulbar involvement	ALS patients randomized to standard care or NPPV baseline PSG at randomization AHI not specified “some obstr events during REM sleep” quality of life measures SALQI	NPPV started in hospital Settings adjusted using daytime ABG, nocturnal oximetry, and NPPV use Goal = normal daytime arterial blood gas	VPAP ST II ST mode (backup rate not specified nasal, oronasal, oral masks IPAP mean 15 EPAP mean 4 IPAP max =24 EPAP max = 5	Compared to standard care, NPPV improved survival and quality of life in the subgroup with better bulbar function Bulbar group – NPPV may improve nocturnal symptoms but not survival
Budweiser²⁵ 2006 Case Series Level IV	RTCD N = 62 initial N = 44 patients available for analysis	Testing during day after NPPV treatment Variable treatment duration but > 3.8 months	NPPV started in hospital Adaptation phase NPPV gradually increased ABG measured twice at night 01:00 AM and 04:00 AM NPPV goals: target tidal volume= 10 cc/kg reduction in PCO₂ 10-15%	nasal or full face mask Pressure NPPV ST mode IPAP = 21.1 ± 3.4 EPAP = 3.1 ± 2.3 PS = 18 ± 3.0 mean respiratory rate = 20.6 bpm Heated humidification if dryness	Improvements in daytime PCO₂, PO₂, lung volumes, and muscle strength changes in daytime PCO₂ was not correlated with duration of use. Improvements in daytime vital capacity (VC) correlated with IPAP Reduction in daytime PCO₂ correlated with PS
Budweiser¹⁸ 2007 Survival of OHS on NPPV Case Series Level IV	OHS N =126 PCO₂ ≥ 45 mm Hg	PSG documents OHS 87 patients, (69%) had OSA NPPV treatment then---> 118 re-evaluated in hospital at 3 to 6 months with daytime and night time ABG	NPPV started in hospital PSG? IPAP increased with goal of reaching a tidal volume of 10 cc/kg ideal body weight Oxygen added only after PS optimized to achieve SaO₂ > 90%	nasal or full face masks BPAP ST IPAP 22.5 ± 3.6 mbar EPAP 5.8 ± 3.1 mbar backup rate 19.2/min	Daytime PCO₂ decreased Adherence (mean) = 6.5 hrs PCO₂ changed Daytime 55.5 ---> 42.1 mmHg Nighttime 59.0 ---> 44.7 mmHg 1, 2, 5 year survival 97%, 92%, 70% all cause-mortality
Chatwin⁶⁰ 2008 Randomized parallel group design inpatient versus out patient initiation of home mechanical ventilation Level II	N = 28 RTCD and NMD Patients with nocturnal hypoventilation	NPPV started in PSG after 2 months of treatment at home After 2 months in hospital overnight monitoring of SpO₂ and transcutaneous PCO₂, as well as daytime ABG Baseline daytime PCO₂ in both groups 44.2 mmHg (inpatient) and 45.7 (outpatient) Baseline peak nocturnal transcutaneous PCO₂: 75 mmHg in outpatient, 71.2 inpatient group	Inpatient – stay sufficient for patient competence Outpatient – 3 visits Outpatient – patient reclined an adjustments made to achieve “good” tidal volume	Pressure preset NPPV Starting settings: Peak insp pressure 16 cm H₂O and backup rate 15-20 bpm Nasal masks used if possible, full face if mouth leak	Improvements in nocturnal SpO₂ similar in both groups Peak nocturnal transcutaneous PCO₂ improved in both groups Daytime PCO₂ decreased in outpatient group Conclusion: outpatient initiation of home ventilation is feasible
De Lucas-Ramos¹⁹ 2004 Case Series Level IV	OHS N = 13 non-consecutive patients	type 3: Home Sleep Testing at baseline 12 mo of NPPV At baseline and after 12 mo NPPV treatment, overnight oximetry, respiratory muscle strength, and mouth occlusion pressure tested	NPPV started in hospital daytime 2 hr adaptation period Initial pressure IPAP = 16, EPAP = 5 then IPAP adjusted during daytime based on arterial blood gas. Nocturnal treatment started IPAP, EPAP	BPAP Nasal mask used end IPAP = 19 ± 2 EPAP of 5 cm H₂O	NPPV--> improved daytime PCO₂, PO₂, FVC, and the mouth occlusion pressure responses to hypercapnia 9/13 needed supplemental oxygen
Ellis²³ 1988 Case Series Level IV	RTCD KS (N = 7)	PSG before and after Rx using Transcutaneous PCO₂ (snoring, ob apn found ) 3 months of treatment	Titration method not specified	nasal mask 5 NPPV (volume cycled) 2 CPAP	NPPV improved sleep quality with lower nocturnal PtcCO₂ Daytime: NPPV increased respiratory muscle strength, improved ABGs, improved lung volumes
Gonzalez²⁴ 2003 Case Series Level IV	RTCD N = 16	1. Baseline PSG 2. NPPV treatment for 36 months 3. At 6 mo PSG OFF NPPV Other outcomes monitored over 3 years	NPPV started in hospital ( Respiratory Care Unit) Adaptation to NPPV during 2-3 hrs in the morning mask, mode settings based on comfort, SaO₂, PtcCO₂ then--> 2 - 3 nights with adjustment of settings based on SaO₂, PtcCO₂ Goal: PCO₂ ≤ 45 mmHg SaO₂ > 90 % either volume vent or BPAP FIO₂ increased if goals not met	Volume cycled NPPV in 7 Pressure cycled NPPV in 9 nasal mask 12, FFM 4 BPAP ST mode IPAP 15 to 22 cm H₂O EPAP 4 mean IPAP = 15 ± 2.8 backup rate 15 bpm Volume vent: Tidal volume = 10-15 cc/kg BF 15-25	Before NPPV PSG AHI = 13.9 After NPPV treatment, PSG (off NPPV) AHI =12.9r SaO₂ improved at night but not sleep efficiency Daytime PO₂, FVC, Resp Muscle strength improved at 36 mo Less hospitalizations Supplemental O₂ at 11pm in 6 patients
Gruis³⁶ 2006 retrospective Assessed Pressure changes needed in chronic NPPV treatment Level IV	NMD 55 total 18 tolerated NPPV 19 intolerant followed classified as NPPV tolerant if > 4 hrs use (?objective) at follow-up visits	Stared NPPV Patients followed 3 of 18 NPPV tolerant patients had symptoms of OSA 2 of 18 NPPV tolerant patients diagnosed with PSG	NPPV started as out patient patient Initial: NPPV 8/3 cm H₂O - changes based on symptoms - most pressure changes occurred in the first year IPAP increased in 2 cm H₂O increments until symptoms improved	Nasal prongs (Nasal Aire) interface Only 6/18 (33%) required PS > 10 cm H₂O 3 ALS has symptoms of OSA PSG found 2 had OSA	18 tolerated NPPV 4 used 8/3 cm H₂O until death Max pressure 19/5 cm H₂O patients with different numbers of pressure changes “for comfort” N = 4 no change 8 single change 4 two changes 1 three changes 1 five changes patients tolerating NPPV had longer survival
Guilleminault⁴⁰ 1998 Case Series Level IV	NMD Muscular dystrophy and others N = 20	1. PSG for diagnosis + MSLT 2. PSG for BPAP titration 3. 4wks NPPV Rx 4. PSG on NPPV + MSLT	PSG for BPAP titration Titration goal: eliminate apnea, hypopnea, hypoventilation	BPAP S (N = 18) BPAP T (N =1) EPAP 5 cm H₂O IPAP 11.5 (9 to 14) cm H₂O	Mean RDI 28.2/hr (8.9); 78% central apnea 19 /20 accepted NPPV Mean Sleep latency (MSLT) increased after NPPV treatment MSL increased from 8.2 minutes to 12 minutes 3 switched to volume ventilators
Guo²¹ 2007 Level IV	OHS Using NPPV for at least 3 months N = 20	PSG during NPPV in patients on chronic NPPV treatment	PSG on NPPV while monitoring machine pressure, mask pressure, airflow, transcutaneous PCO₂ Note transcutaneous CO₂ device calibrated with calibration gas before each measurement night	nasal (17) or full face masks (3), 4 also on supplemental oxygen BPAP ST mode used mean IPAP = 18.5 ± 4.6 mean EPAP = 6.2 ± 1.4 mean backup rate = 13.7 ± 2.2 bpm	55% had desynchronization 40% frequent periodic breathing auto-triggering uncommon but frequent in a single patient
Janssens¹⁰ 2008 assess effect of volume targeted BPAP on sleep quality Randomized cross over Level II for VT-BPAP	OHS stable on chronic NPPV N = 12	NPPV using current settings one night and VT-BPAP on the other night PSG with Ptc CO₂ VT-BPAP adjusted during day to find tolerated settings	no titration studied at current settings chronic settings (cmH₂O): IPAP = 21.6 ± 4.7 EPAP 8.6 ± 2.7 backup rate 13.3 ± 2.0 range (10-17) bpm	9 FFM, 3 nasal masks ST mode VT 7-8 cc/kg IPAPmax = 30 cm H₂O IPAPmin = usual IPAP - 3 Backup rate same as chronic treatment	mean tidal volume, ventilation, IPAP higher with VT-BPAP – all small differences Slight improvement in nocturnal PCO₂ on VT-BPAP compared BPAP amounts of stage N2 and TST better with BPAP than VT-BPAP Better subjective sleep quality on BPAP WASO higher with VT-BPAP critique = lack of adaptation to VT-BPAP
Katz⁴⁴ 2002 Case Series Level IV	children NMD Spinal muscular atrophy, DMD, myotonic dystrophy, myopathies N = 15	PSG for Diagnosis PSG baseline AHI = 7.3/hour PSG for BPAP titration then follow-up In 9 PSG repeated at follow-up	NPPV titration with PSG PtcCO₂ used NPPV Goal: a decrease of at least 10 mmHg if PtcCO₂ was > 50 mmHg normalize respirations and SaO₂	nasal mask nasal pillows IPAP 9 – 20 cm H₂O EPAP 3-6 backup rate set at 10% below resting breathing rate	Post NPPV initiation children spent 85% fewer days in hospital PSG repeated on NPPV Nocturnal PtcCO₂ normalized AHI decreased
Leger²⁹ 1994 Case Series Level IV	Mixed population with CAH KS post TB sequelae MD, COPD N= 276	NPPV started in hospital after exacerbation Long term f/u	NPPV started in hospital after exacerbation Titration details not specified Humidity in 1/3	customized nasal masks volume ventilation 12=15cc/kg tidal volume assist-control or control mode breaths per minute 15 to 16	KS, post TB improved quality of life and daytime gas exchange, less hospital days MD – less continued NPPV, did reduce hospital days Side effects dryness, gastric distension, nasal congestion, eye irritation, nasal bridge soreness
Masa¹⁶ 2001 compare NPPV treatment in OHS vs RTCD Cohort study Level IV	OHS N =22 PCO₂ > 47 RTCD (KS) N = 14 PCO₂ > 47	PSG, if AHI < 20/hr admitted to hospital for protocol re-evaluation after 4 months of NPPV	NPPV started in hospital Titration details not provided Adaptation to NPPV 3 to 7 days Goal: maximal reduction in PCO₂ and maintenance of SaO₂ > 90%. 11 OHS, 8 KS required oxygen supplement at start of study --> at end only 2 OHS using supplemental oxygen at night	Volume cycled ventilator in most, BPAP in 5 OHS, 1 KS	OHS group daytime PCO₂ decreased from 58 to 45 mmHg RTCD group: daytime PCO₂decreased from 59 to 45 mmHg after treatment, no change in muscle strength or PFTs Both OHS and RTCD had equivalent improvement in symptoms and daytime gas exchange with NPPV treatment Conclusion: NPPV effective in OHS
Masa³¹ 1997 Oxygen vs NPPV Crossover trial not randomized order Level II	RTCD 8 7KS+1 thoracoplasty 2 NMD 11 OHS No daytime hypercapnia. 27 nocturnal desaturators without OSA 21 completed the protocol	baseline PSG to demonstrate desaturation without OSA RTCD patients had AHI 5.6/hour overall but 19 ± 17/hour during REM sleep. 2 wks of nocturnal oxygen then PSG on oxygen then 2 wks nocturnal NPPV then PSG on NPPV	NPPV started in hospital Adaptation period 3 to 7 days. The protocol was not specified	BPA P N = 7 Volume cycled ventilator N=20	NPPV not oxygen normalized nocturnal hypoventilation and improved symptoms oxygen treatment had greater nocturnal saturation Daytime PO₂ improved only after NPPPV Conclusion: RTCD patients without daytime hypoventilation but with nocturnal hypoventilation and desaturation obtain more benefit from NPPV than nocturnal oxygen
Mellies⁴² 2003 Case Series Level IV	NMD children N = 30	1. PSG for dx 2. PSG for titration 3. Follow-up RDI 10.5 ± 13.1 REM RDI 20.5 ±21.1	NPPV titration using PSG BPAP ST mode goals: suppress SDB, SaO₂ > 95%, PtcCO₂ < 50 mmHg PetCO₂ used, calibrated before each study	Full face mask (10) nasal masks, others IPAP 13.9 range (8-19) EPAP 4.4 range (3-8) backup rate 19.6 (14-24) bpm	Improvement in daytime PCO₂ and PO₂ Improvement in TST with PCO₂ > 50 or TST with SAO₂ < 90%
Perez de Llano¹² 2005 Retrospective Study Case Series Level IV	OHS started on NPPV 20 elective 34 after exacerbation	NPPV treatment then follow-up PSG performed once stable and discharged from the hospital	NPPV started in hospital PSG not used for titration daytime sessions for exacerbations night time session for all starting EPAP= 6 cmH₂O, IPAP=10 titrated upward adjusted based on nocturnal SaO₂	nasal mask At discharge: N=3 CPAP N=2 vol vent N= 49 BPAP mean IPAP=18 (12-30) mean EPAP = 9 (5-13) N=47 needed supplemental oxygen	AHI > 5 in 87% 47% required supplemental oxygen ESS decreased from 16 to 6 mean decrease in daytime PCO₂ was 17 mmHg PCO₂ fell after discharge from hospital on treatment: not necessary to totally normalize PCO₂ – continued improvement occurs over time
Perez de Llano¹⁴ 2008 Level IV assess those who can be switched to CPAP after NPPV	OHS N = 24 N=11 CPAP N=13 NPPV	OHS stabilized on NPPV When clinically stable had PSG titration starting with CPAP, changed to BPAP and oxygen added if needed.	NPPV titration by PSG CPAP used to eliminate obstructive events. If low SaO₂ persisted BPAP used EPAP = CPAP and IPAP increased up to 20 to improve SaO₂. If not effective supplemental oxygen was added	CPAP group mean pressure 10.4 cm H₂O NPPV group 11 BPAP, 2 volume vent. Pressures not presented	CPAP group had higher AHI and worse SaO₂ NPPV group had lower AHI and worse SaO₂
Piper and Sullivan²⁶ 1996 Does NPPV at night improve spontaneous ventilation during sleep (i.e., NPPV)? Case Series Level IV	NMD 8 RTCD 6 N = 14	1. Baseline PSG before 2. 6 mo NPPV treatment Ventilator settings verified during PSG before discharge from hospital 3. Sleep study OFF NPPV after 6 mo or greater treatment.	NPPV started in hospital NPPV protocol not clearly specified, NPPV adjusted based on patient tolerance, adjusted with nocturnal oximetry NPPV settings verified by PSG before discharge	nasal mask 13 patients volume ventilator 1 patient pressure ventilator	Daytime Chronic NPPV improved spontaneous daytime PO₂ and PCO₂ and muscle strength Night time: chronic NPPV improved nocturnal SaO₂ and transcutaneous PCO₂ during sleep (off treatment)
Piper²² 2007 RCT Level I CPAP vs BPAP	OHS stable awake PCO₂ > 45, pH > 7.34 18 CPAP 18 BPAP	Initial CPAP trial in all subjects -- excluded those with persistent nocturnal hypoxemia or CO₂ retention despite CPAP those on BPAP had an additional PSG for BPAP titration compared long term rx with CPAP versus BPAP over 3 months	NPPV titration with PSG starting EPAP = effective CPAP -2 (minimum 5) starting IPAP such that PS =4. EPAP increased in 1 cm H₂O increments if inspiratory efforts did not trigger IPAP IPAP increased to eliminate hypopneas and improve SaO₂	CPAP mean pressure was 14 cm H₂O BPAP S mode mean IPAP = 16 cm H₂O EPAP = 10 cm H₂O 7 patients on supplemental oxygen	Both groups decrease in daytime PCO₂ – no difference between CPAP and BPAP Similar improvements in ESS, PVT, Adherence
Redolfi²⁰ 2006 Leptin in OHS prospective case controlled Level IV	OHS N = 6	1. Type 3 monitor used excluded OHS patients with OSA (AHI > 5.hr) 2. Leptin before and after 10 months of NPPV 3. Results compared with 6 eucapnic obese subjects	Location where NPPV started is unclear (hospital or clinic?). EPAP =4 IPAP adjusted on basis of overnight oximetry until SaO₂ > 90%, if higher IPAP not tolerated supplemental oxygen was addded Type 3 device on NPPV to evaluate settings.	BPAP Synchrony device mean pressures IPAP = 12 EPAP = 4	Daytime PO₂ increased, PCO₂ decreased leptin increased
Ramesh³³ 2008 Case Control Level IV	Congenital Central Hypoventilation Syndrome N = 15 age range 9 months to 21 years	9 patients started NPPV at later age 6 patients started NPPV at 5 to 26 weeks of age 3 with positive pressure ventilation via endotracheal tube, 1 on positive pressure ventilation via tracheosotomy	NPPV protocol not presented	nasal and face masks Details of pressures used not presented	NPPV started at later age took median of 3 years to wean from former mode of ventilation to mask ventilation
Simonds²⁸ 2006 Case Series Level IV	NMD or RTCD N = 40 children 17 daytime resp failure 18 nocturnal hypoventilation 3 being weaned 2 frequent chest infections	overnight SaO₂, Ptc CO₂ monitoring, some had full PSG monitoring repeated once NPPV settings finalized	NPPV started in hospital NPPV settings determined by overnight SaO₂, PtcCO₂ monitoring, supplemental oxygen if needed	BPAP in ST mode 20 ffm, 18 nasal masks, 2 nasal pillows mean pressures not given	38 of 40 tolerated mask ventilation Nocturnal: peak PtcCO₂ decreased, mean and minimum PO₂ improved
Storre⁸ 2006 AVAPS (Average Volume Assured Pressure Support) Randomized Crossover Level II AVAPS vs BPAP ST	OHS N = 10 “Non-responders” to CPAP	1. 6 weeks of AVAPS or BPAP-ST then PSG 2. 6 weeks of alternate mode then PSG	NPPV settings according to daytime and nighttime tolerance and to maximally decrease PtcCO₂	AVAPS IPAPmax = 30 mbar target volume 7 to 10 cc/kg BPAP ST IPAP up to 20 mbar EPAP 4 to 8 mbar both modes: backup rate = 12 to 18 bpm I/E 1 : 2	Sleep quality and oxygen saturation, quality of life equivalent between AVAPS and BPAP ST Daytime PCO₂ after 6 weeks slightly lower on AVAPS Nocturnal PtcCO₂ lower on AVAPS mean difference 6.9 mm Hg
Tibballs³² 2003 Case Series Level IV	Congenital Central Hypoventilation N = 4	2 newborns treated with nasal mask and BPAP when parents refused tracheostomy 2 older children transitioned trach /volume ventilator to nasal mask BPAP	Titration protocols not specified Case # 1 NPPV tried at age 5 and 6 unsuccessful mask not tolerated, age 9 tried not successful, tried again age 11 successful, tracheostomy removed on BPAP phrenic pacing during the day Case #2 BPAP 24/4 ST mode with 12 bpm backup	Nasal masks Case # 3 developed mid-face hypoplasia uses negative pressure ventilator most nights, for travel BPAP used Case #4 BPAP started at age 9 months, developed mid-face hypoplasia, at age 3 years used combination of BPAP to fall asleep and negative pressure ventilator for most of night	2 cases mid-face hypoplasia developed then switched to negative pressure ventilator for at least part of treatment maxilla may fail to grow in relation to mandible- lower jaw protrudes “pseudoprognathism”
Toussaint³⁷ 2008 Prospective Case Series Level IV	NMD Duchenne muscular dystrophy group 1: no dyspnea, no support group 2: nocturnal hypercapnia group 3: nocturnal NPPV, no breathlessness group 4: nocturnal NPPV with breathlessness group 5 using 24 hr NPPV	group 4 nightly NPPV but no breathlessness TT0.1 tension time index a measure of muscle load measured at 20:00 and at 8:00 after NPPV	Not specified tidal volume 12 cc/kg then reduced slowly goal maintain normocapnia	NPPV Volume ventilator mean tidal volume 653 ml, mean RR 19.9	Tension time index higher with greater weakness group 1 to 3 not improvement in tension time index after overnight NPPV group 4 and 5 showed significant reduction in tension time index after overnight NPPV NPPV improved AM muscle function
Tuggey and Elliot²⁷ 2005 Randomized Crossover pressure versus volume ventilation Level II for type of NPPV	RTCD N = 13	Randomized crossover design after treatment for 4 weeks, PSG on NPPV with either pressure or volume mode Volume vs Pressure NPPV compared	No EPAP provided daytime titration either pressure or volume ventilation adjusted to give equivalent minute ventilation Volume ventilatory = tidal volume increased in 100 cc increments IPAP increased in increments of 5 cm H₂O between limits of 10 and 40 cm	TV pressure/Volume to 548/.546 Pressure mode backup rate =15 IPAP =25 cm H₂O RR =15 Volume mode: backup rate 15 TV 749 ml	Night time: 2 modes provided equivalent sleep quality and SaO₂, Daytime: 2 modes resulted in equivalent respiratory muscle strength, health status, ABGs, and daytime function Pressure NPPV showed more leak and lower ventilation Pressure and volume ventilation modes showed lower ventilation during sleep than wake titration
Tuggey⁷² 2006 comparing titration goal of respiratory muscle rest and reverse nocturnal hypoventilation Level II for titration goal	N = 24 12 COPD 12 RTCD	daytime study Increase in pressure or tidal volume Pressure time product measured with esophageal balloon (PTPes)	Pressures above 20-25 cm H₂O or volumes above 6 cc/kg did not produce further drops in PTPes, ventilation did continue to increase although so did leak	Nasal mask Volume ventilator Pressure ventilator	Little gain in increasing PS above 20 in RTCD Respiratory effort minimized below maximum ventilation
Vianello⁴³ 1994 Case controlled Level IV	NMD Duchenne Muscular Dystrophy N = 5 on NPPV but 10 in total	compared 5 with NPPV with another 5 without NPPV but similar characteristics (case control)	NPPV started in the Hospital 3 consecutive nights with overnight NPPV monitoring with transcutaneous PCO₂ monitoring NPPV adjusted so PtcCO₂ < 45	Volume Ventilator used Nasal mask	at 24 months 4/5 non NPPV had died 0/5 NPPV group had died at 6 months drop in FVC much lower in NPPV group
Ward³⁰ 2005 Randomized controlled trial standard care vs NPPV Manually adjusted overnight with SaO₂, tcPCO₂ ? EEG Level II	NMD RTCD N = 26 daytime normocapnia and nocturnal hypercapnia most actually MD	Baseline “overnight respiratory sleep study” including SaO₂ and PtcCO₂ Randomized patients to control or NPPV 12 randomized to control, 2 drop outs 13 randomized to NPPV but 3 elected not to start NPPV Studied every 6 months tcPCO₂, SaO₂ Control group followed, if met safety criteria started on NPPV	NPPV adjusted by overnight “monitoring” separate from initial diagnostic with PSG. Uncertain if overnight monitoring means PSG Goal of overnight monitoring to adjust NPPV to normalize SaO₂ and PCO₂	BPAP ST mode pressures not presented nasal or full face masks	Nocturnal PtcO₂ decreased in NPPV group 9 /10 in control group deteriorated and treated with NPPV after 8 months
Windisch ⁵⁵ 2005 Cross-over trial Volume vs pressure preset ventilation Level II	N = 15 9 COPD 6 Non-COPD OHS, achondroplasia, post-polio,post-TB, ALS, Duchenne MD Chronic hypercapnia 5 patients did not complete study	Received either volume or pressure preset ventilation via mask for 6 weeks, then switched to alternate mode PSG used to assess sleep quality with transcutaneous PCO₂ monitoring Volume NPPV (V-NPPV) and pressure NPPV (P-NPPV) compared	Admitted to hospital for start of NPPV NPPV adjusted to NPPV adjusted to achieve maximal decrease in PCO₂ Supplemental oxygen added to keep SpO₂ > 90% Arterialized ear lobe blood tested	ST/Assist control mode Nasal mask interface Passive humidification Mean values: In pressure mode set peak pressure = 26.6, delivered peak pressure = 22.9 (mbar) Respiratory rate = 20.5 Volume set = 677 ml	Night time PCO₂ decreased in both modes Baseline 54.6 mmHg P-NPPV 46.5 mm Hg V-NPPV 46.2 mmHg Similarly small decrease in daytime PCO₂ in P-NPPV and V-NPPV similar Comparable improvements in sleep quality in both modes More gastric distension in volume mode

RTCD refers to restrictive chest wall disease; NMD, neuromuscular disease; KS, kyphoscoliosis; OHS, obesity hypoventilation syndrome; FFM, full face mask (oronasal); VT-BPAP, volume targeted BPAP; CAH, chronic alveolar hypoventilation; vs, versus; PtcCO₂, transcutaneous PCO₂. IPAP and EPAP in cm H₂O unless specified.